e-PTFE porous tubes made by stretching and sintering have been used as tubular prostheses for artificial blood vessels for a number of years. These polymeric tubes have certain advantages over conventional textile prostheses, but also have disadvantages of their own. The e-PTFE tube has a microporous structure consisting of small nodes interconnected with many thin fibrila. The diameter of the fibrils, which depend on the processing conditions, can be controlled to a large degree and the resulting flexible structure has greater versatility in many aspects than conventional textile grafts. For example, e-PTFE grafts can be used in both large diameter, i.e. 6 mm or greater artificial blood vessels, as well as in diameters of 5 mm or less.
One particular problem, however, with expanded PTFE tubes, is their tendency to leak blood at suture holes and often propagate a tear line at the point of entry of the suture. As a result, numerous methods of orienting the node and fibril structure have been developed to prevent tear propagation. These processes are often complicated and require special machinery and/or materials to achieve this end.
Additionally, expanded PTFE arterial prostheses have been reported as suffering from poor, cellular infiltration and collagen deposition of the microporous structure by surrounding tissue. Numerous attempts to achieve improved blood compatibility and tissue binding properties have thus far fallen short. For example, in a study reported by Guidoin, et al., "Histopathology of Expanded PTFE", Biomaterials 1993, Volume 14, No. 9, cellular infiltration of the e-PTFE microporous structure was observed as being minimal. In an attempt to produce instant endothelial cell monolayers on graft surfaces, cryopreserved cultivated human saphenous vein endothelial cells were cultivated on reinforced PTFE prostheses. Prior to seeding of the endothelial cells on the prosthesis, the graft surface was precoated with human fibronectin. This study, reported by Kadletz, et al. in "Invitro Lining of Fibronectin Coated PTFE Grafts With Cryopreserved Saphenous Vein Endothelial Cells", Thorac. Cardiovasc. Surgeon 35 (1987) 143-147, reported discouraging results. More recently a study using laminin, collagen type I/III as well as fibronectin as precoating materials prior to seeding of endothelial cells on e-PTFE grafts was performed by Kaehler, et al., reported in "Precoating Substrate and Surface Configuration Determine Adherence and Spreading of Seeded Endothelial Cells on Polytetrafluoroethylene Grafts", Journal of Vascular Surgery, Volume 9, No. 4 April (1989). This study reported that cell adherence and cell spreading were distinctly superior on the surfaces which were precoated with fibronectin/type I/III collagen.
Thus far, e-PTFE substrates still suffer from endothelial cell adherence problems. The present invention is an attempt to address this problem, along with the problem of suture hole bleeding, by introducing into the porous walls of the e-PTFE prosthesis a solid natural material such as collagen, gelatin or derivatives of these materials. In addition to the above advantages, material such as collagen also serves to denucleate e-PTFE. Denuclearization removes air pockets and therefore reduces the thrombogenicity of the e-PTFE surface. Thus, the present invention seeks to improve prosthesis assimilation into the surrounding tissue, enhance the healing process as well as provide a more blood-tight prosthetic implant.
More recently, materials such as collagen and gelatin have been applied as coatings or as impregnations to textile grafts to avoid the need for preclotting the textile substrate prior to implantation. For example, U.S. Pat. Nos. 3,272,204, 4,842,575 and 5,197,977 disclose synthetic vascular grafts of this nature. Additionally, the '977 patent includes the use of active agents to enhance healing and graft acceptance once implanted in the body. The collagen source used in these patents is preferably from bovine skin or tendon dispersed in an aqueous solution that is applied to the synthetic textile graft by massaging or other pressure to cover the entire surface area and/or penetrate the porous structure.
U.S. Pat. No. 4,193,138 to Okita discloses a composite structure comprising a porous PTFE tube in which the pores of the tube are filled with a water-soluble polymer. The water-soluble polymer is used to form a hydrophilic layer which imparts an anti-thrombogenic characteristic to the e-PTFE tube. Examples of such polymers are polyvinylalcohol, polyethylene oxides, nitrogen-containing polymers and avionic polymers such as polyacrylic acid and polymethacrylic acid. Additionally, hydroxy esters or carboxy esters of cellulose and polysaccarides are also disclosed. This patent describes the diffusion of the water-soluble polymer into the pores of the tube and subsequent drying. The water-soluble polymer is then subjected to a cross-linking treatment to render it insoluble in water. Cross-linking treatment such as heat treatment, acetalization, esterification or ionizing radiation-induced cross-linking reactions are disclosed. The water-soluble materials disclosed in this patent are synthetic in nature.